1. Field of the Invention
This application is directed generally to methods of treating prostate cancer, polycystic ovarian disease, benign prostatic hypertrophy, and precocious puberty.
2. Related Art
Mullerian inhibiting substance (MIS) is a member of the transforming growth factor-xcex2 (TGFxcex2) family of growth and differentiation factors. After the sexually indifferent gonad commits to testis development under the influence of the testis-determining factor, SRY, Sertoli cells of the fetal testis begin procuring MIS, which is a phenotypic hallmark of testis development (Swain et al., Nature 391:761-767 (1998)). MIS, also known as anti-Mullerian hormone (Jossa et al., Recent Prog. Horm. Res. 48: 1-59 (1993)), is absolutely required for normal male reproductive tract development because it affects the regression of the Mullerian duct of the bipotential urogenital ridge, which, is left undisturbed, would give rise to female reproductive tract structures such as the uterus, Fallopian tubes, and upper vagina (Jost, A., Arch. Anal. Microsc. Morphol. Exp. 36:271-315 (1947); Cate et al., Cell 45:685-698 (1986); Teixeira and Donohoe, J. Androl. 17:336-341 (1996)). Adult ovaries and testes also produce MIS, albeit at much lower levels than in fetal males, and the functional roles played by MIS in these settings have not been fully elucidated (Ueno et al., Endocrinology 123:1652-1659 (1988); Tsafriri et al., Biol. Reprod. 38:481-485 (1988)). However, studies in the rat suggest a role for MIS in oocyte maturation (Takahashi et al., Mol. Cell Endocrinol. 47:225-234 (1986)) and in human ovary in blocking granulosa cell proliferation and reducing steroidogenesis (Kim et al., J. Clin. Endocrinol. Metab. 75:911-917 (1992), Seifer et al., J. Clin. Endocrinol. Metab. 76:711-714 (1993)).
The present invention provides a method of treating a condition or disease characterized by an excess of one or more androgens, the method comprising administering an effective amount of MIS to a patient.
The present invention also provides a method of treating a condition or disease characterized by an excess of one or more androgens, the method comprising administering an effective amount of a nucleic acid encoding MIS to a patient.
The present invention also provides a method of decreasing the plasma level of one or more androgens, the method comprising administering to a patient an effective amount of MIS, wherein the amount of MIS is sufficient to decrease the plasma level of the one or more androgens below the normal level for the one or more androgens.
The present invention also provides a method of decreasing the plasma level of one or more androgens, the method comprising administering to a patient an effective amount of nucleic acid encoding MIS, wherein the amount of MIS is sufficient to decrease the plasma level of the one or more androgens below the normal level for the one or more androgens.
The methods of the present invention are particularly well-suited for the treatment of prostate cancer, polycystic ovarian disease, benign prostatic hypertrophy, and precocious puberty.